Neural regulation of the homeostasis depends on healthy synaptic function. Adaptation of synaptic functions to physiological needs manifests in various forms of synaptic plasticity (SP), regulated by the normal hormonal regulatory circuits. During the past several decades, the hormonal regulation of animal and human organisms have become targets of thousands of chemicals that have the potential to act as agonists or antagonists of the endogenous hormones. As the action mechanism of these endocrine disrupting chemicals (EDCs) came into the focus of research, a growing number of studies suggest that one of the regulatory avenues of hormones, the morphological form of SP, may well be a neural mechanism affected by EDCs. The present review discusses known and potential effects of some of the best known EDCs on morphological synaptic plasticity (MSP). We highlight molecular mechanisms altered by EDCs and indicate the growing need for more research in this area of neuroendocrinology.

Background: Gold nanoparticles (AuNPs) have several beneficial properties that make them effective as intracellular drug carriers, and their potential for various diagnostic and therapeutic applications is gaining recognition. Depending on their size and shape, AuNPs can cross the central nervous system (CNS) through the blood–brain barrier (BBB). In the CNS, they can exert a variety of influences on neuronal and glial cells, which can be both supportive—promoting cell health and function—and cytotoxic, potentially leading to cellular damage. The hypothalamus (HT) is the first region where nanoparticles (NPs) interact, as this neuroendocrine center is particularly sensitive to factors in the systemic circulation due to its function and location. This area is affected by systemic factors, including pro-opiomelanocortin (POMC) neurons, which regulate metabolic function and maintain homeostasis. The activity of mitochondria within these cells influences their response to both external factors and the presence of AuNPs, thereby facilitating a complex interplay between nanoparticle interactions and cellular metabolism in this vital brain region. Aims: This study investigates how AuNPs, at different concentrations and exposure times under in vitro conditions, affect the mitochondrial activity of POMC neurons, aiming to provide a comprehensive understanding of the mechanisms in the HT. Methods: The study investigates the effect of varying gold nanoparticle concentrations on the mitochondrial activity of POMC neurons over treatment periods of 1, 15, 24, and 48 h. Mitochondrial activity was measured using a Seahorse XFp Analyzer to provide high-resolution insights. Additionally, mitochondrial functionality was assessed through the detection of reactive oxygen species (ROS) and cell viability. Results: The findings indicated that the effects of gold nanoparticles on mitochondrial activity depend significantly on their concentration and exposure time. Specifically, exposure leads to an increase in early response systems, the citric acid cycle, and proton efflux, ultimately resulting in the inhibition of mitochondrial function and ATP production in POMC cells. This disruption may affect hypothalamic regulation and energy metabolism.

Extracellular vesicles (EVs) are key mediators of intercellular communication across biological kingdoms, with central roles in immune regulation and disease processes. Despite shared structural features, EVs derived from bacteria, plants, and mammalian cells differ substantially in their biogenesis, molecular composition, and immunological functions. EV formation pathways generate vesicles with distinct cargo profiles, including pathogen-associated molecular patterns (PAMPs) in bacterial EVs, regulatory small RNAs in plant-derived vesicles, and cytokines, microRNAs, and antigen-presenting complexes in mammalian EVs. Differences in cargo result in divergent immune outcomes. Bacterial EVs predominantly activate innate immunity via pattern recognition receptors such as Toll-like receptors, whereas plant-derived EVs exhibit low immunogenicity and mediate cross-kingdom RNA interference. In contrast, mammalian EVs primarily regulate immune responses by modulating antigen presentation and cytokine signaling. These findings support a framework in which EV origin determines immunological function and therapeutic applicability. This perspective highlights the importance of selecting appropriate EV sources for vaccine development, regenerative medicine, and targeted delivery strategies, while addressing current challenges related to heterogeneity, standardization, and safety.

• Mitochondria respond before mRNA changes, reflecting early metabolic stress. • U-shaped receptor mRNA response hints at complex BPA dose-dependency. • Low-dose BPA rapidly upregulates hypothalamic PPARγ without altering ERα or TRα.